Glucose fluorescence monitor and method

• US 5,341,805 A
• Filed: 04/06/1993
• Issued: 08/30/1994
• Est. Priority Date: 04/06/1993
• Status: Expired due to Term

• Current Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Original Assignee: Cedars-Sinai Medical Center (Cedars Sinai Health System)
• Inventors: Stavridi, Marigo, Grundfest, Warren S.
• Primary Examiner(s): Sykes, Angela D.
• Application Number:
  US08/043,580
• Time in Patent Office: 511 Days
• Field of Search: 128/633.5, 128/664-667, 128/645-652, 128/745, 351/206-207, 351/221, 356/39-41, 356/317-320
• US Class Current: 600/316
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/0075 by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy A61B5/0071 takes precedence
• CPC Class Codes: A61B 5/0084 for introduction into the body, e.g. by catheters A61B5/1459 takes precedence
• CPC Class Codes: A61B 5/0088 for oral or dental tissue
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: G01N 21/6402 Atomic fluorescence; Laser induced fluorescence
• CPC Class Codes: G01N 21/6486 Measuring fluorescence of biological material, e.g. DNA, RNA, cells G01N21/6428 takes precedence

Abstract

A glucose monitor, and related method, determines the concentration of glucose in a sample by monitoring fluorescent light produced directly by any glucose present in the sample. The glucose monitor illuminates the sample with ultraviolet excitation light that induces any glucose present in the sample to fluoresce, with the fluorescent light being monitored and processed to determine the concentration of glucose in the sample. A sensor monitors the return light, which includes fluorescent light produced by any glucose in the sample, and generates first and second electrical signals indicative of the intensity of light in two wavelength bands. One wavelength band includes a characteristic spectral peak of glucose fluorescence, and the other wavelength band is a reference band having known spectral characteristics. A processor then processes the first and second electrical signals to determine the concentration of glucose in the sample. A fiber-optic waveguide is used to guide the excitation light from the laser light source to the sample and the return light from the sample to the sensor. The fiber-optic waveguide is housed in a catheter or probe that is adapted to monitor the concentration of glucose percutaneously in the oral cavity tissues of a person'"'"'s mouth such as the gums.

Claims

1. Apparatus for determining the concentration of glucose in a sample, comprising:

a light source that emits excitation light that is directed at a sample to produce return light from the sample, such return light including fluorescent light produced by any glucose present in the sample;

a sensor that monitors the return light and generates a glucose fluorescence signal indicative of the intensity of return light within a wavelength band associated with the direct fluorescence of glucose and generates a reference signal indicative of the intensity of return light within a reference wavelength band; and

a processor that processes the glucose fluorescence signal and the reference signal to determine the concentration of glucose in the sample.

2. Apparatus for determining the concentration of glucose in a sample, comprising:

a light source that emits narrowband excitation light that is directed at a sample to produce return light from the sample, the excitation light having a wavelength between about 250 nanometers and about 350 nanometers;

a sensor that monitors the return light and generates a first signal indicative of the intensity of return light within a first wavelength band, the first wavelength band being within a range that is about 30 to 50 nanometers longer than the wavelength of the excitation light, and wherein the sensor also generates a second signal indicative of the intensity of return light within a second wavelength band, the second wavelength band extending from about 380 nanometers to about 420 nanometers; and

a processor that processes the first and second signals to determine the concentration of glucose in the sample.

3. Apparatus for determining the concentration of glucose in a sample as defined in claim 2, wherein:

the wavelength of the excitation light is about 308 nanometers;

the first wavelength band extends from about 335 nanometers to about 355 nanometers; and

the second wavelength band extends from about 380 nanometers to about 420 nanometers.

4. Apparatus for determining the concentration of glucose in a sample as defined in claim 2, and further comprising one or more waveguides transmitting the excitation light from the light source to the sample and transmitting the return light from the sample to the sensor.

5. Apparatus for determining the concentration of glucose in a sample as defined in claim 4, wherein the one or more waveguides comprises:

a first fiber-optic waveguide transmitting the excitation light from the light source to the sample; and

a second fiber-optic waveguide transmitting the return light from the sample to the sensor.

6. Apparatus for determining the concentration of glucose in a sample as defined in claim 5, and further comprising a probe housing the one or more fiber-optic waveguides.

7. Apparatus for determining the concentration of glucose in a sample as defined in claim 6, wherein the probe is a catheter adapted to be placed in an extracorporeal blood flow.

8. Apparatus for determining the concentration of glucose in a sample as defined in claim 2, wherein the sensor includes:

a first detector that detects the return light within the first wavelength band and generates the first signal; and

a second detector that detects the return light within the second wavelength band and generates the second signal.

9. Apparatus for determining the concentration of glucose in a sample as defined in claim 2, wherein the sensor includes:

a spectrograph having an array of detectors, the spectrograph resolving the return light such that each detector of the array detects a different spectral wavelength of the return light and generates a separate electrical signal representing the intensity of light in its wavelength; and

an optical analyzer that analyzes the plurality of electrical signals from the spectrograph and generates the first and second signals.

10. Apparatus for determining the concentration of glucose in a sample as defined in claim 2, wherein the sensor comprises:

a dichroic filter that rejects the return light having a wavelength equal to the wavelength of the excitation light and transmits the return light within the first and second wavelength bands;

a stop having a slit aperture, wherein a portion of the return light that is transmitted through the dichroic filter passes through the slit;

a prism that spreads the return light that passes through the slit such that the return light is spread along an axis by a distance proportional to the wavelength of the return light; and

first and second electro-optical detectors that generates the first and second signals, respectively, the first electro-optical detector located along the axis at a distance corresponding to the first wavelength band and the second electro-optical detector located along the axis at a distance corresponding to the second wavelength band.

11. A method of determining the concentration of glucose in a sample, comprising:

directing excitation light at a sample to cause the sample to produce return light, such return light including fluorescent light produced by any glucose present in the sample;

monitoring the return light and generating first and second signals, the first signal indicative of the intensity of the return light within a first wavelength band and the second signal indicative of the intensity of return light within a second wavelength band; and

processing the first and second signals to determine the concentration of glucose in the sample.

12. A method of determining the concentration of glucose in a sample, comprising:

directing narrowband excitation light having a wavelength between about 250 nanometers and about 350 nanometers at a sample to cause the sample to produce return light, such return light including fluorescent light produced by any glucose present in the sample;

monitoring the return light and generating first and second signals, the first signal indicative of the return light within a first wavelength band, the first wavelength band being within a range that is about 30 to 50 nanometers longer than the wavelength of the excitation light, and the second signal indicative of the intensity of return light within a second wavelength band;

the second wavelength band extending from about 380 nanometers to about 420 nanometers; and

processing the first and second signals to determine the concentration of glucose in the sample.

13. A method of determining the concentration of glucose in a sample as defined in claim 12, wherein:

the wavelength of the excitation light used in the step of directing is about 308 nanometers;

the first wavelength band used in the step of monitoring extends from about 335 nanometers to about 355 nanometers; and

the second wavelength band used in the step of monitoring extends from about 380 nanometers to about 420 nanometers.

14. A method of determining the concentration of glucose in a sample as defined in claim 12, wherein the step of directing excitation light at a sample further comprises the step of guiding the excitation light to the sample.

15. A method of determining the concentration of glucose in a sample as defined in claim 12, wherein the step of monitoring the return light further comprises the step of guiding the return light from the sample.

16. A method for determining the concentration of glucose in a sample as defined in claim 12, wherein the step of monitoring the return light further comprises:

detecting the return light within the first wavelength band to generate the first signal; and

detecting the return light within the second wavelength band to generate the second signal.

17. A method of determining the concentration of glucose in a sample as defined in claim 16, wherein the step of monitoring the return light further comprises the step of resolving the return light into its different spectral wavelengths to detect the light within the respective first and second wavelength bands.

18. Apparatus for determining the concentration of glucose in the tissues of a person'"'"'s mouth, comprising:

a light source that emits excitation light;

a first fiber-optic waveguide transmitting the excitation light from the light source to the tissues of a person'"'"'s mouth to cause the tissues to produce return light, such return light including fluorescent light produced by any glucose present in the tissues;

a sensor that monitors the return light;

a second fiber-optic waveguide transmitting the return light from the tissues of the mouth to the sensor, wherein the sensor generates a glucose fluorescence signal indicative of the intensity of return light within a wavelength band associated with the direct fluorescence of glucose and generates a reference signal indicative of the intensity of return light within a reference wavelength band; and

a probe housing the first and second fiber-optic waveguides, wherein the probe is adapted to enter the mouth; and

a processor that processes the glucose fluorescence signal and the reference signal to determine the concentration of glucose in the tissues of a person'"'"'s mouth.

19. A method of determining the concentration of glucose in a sample, comprising:

directing excitation light at a sample to cause the sample to produce return light, such return light including fluorescent light produced by any glucose present in the sample;

monitoring the return light and generating a glucose fluorescence signal and a reference signal, the glucose fluorescence signal indicative of the intensity of the return light within a wavelength band associated with the direct fluorescence of glucose and the reference signal indicative of the intensity of return light within a reference wavelength band; and

processing the glucose fluorescence signal and the reference signal to determine the concentration of glucose in the sample.